PROJECT SUMMARY/ABSTRACT In US adults, there are large, unexplained racial disparities in hypertension (HTN), a leading cause of morbidity and mortality. We propose to distinguish the relative contribution of sleep and circadian mechanisms to the increased risk for HTN in African American (Black) adults compared to European American (White) adults. The scientific premise for the proposed research, based partly on our recent work, is that both sleep and circadian mechanisms contribute to blood pressure (BP) regulation and HTN, and both sleep and circadian regulation differ between Black and White races. The innovation is to understand to what degree these sleep and circadian factors mechanistically explain this racial disparity in HTN. Recent work shows that Blacks have poorer sleep and a shorter circadian period, resulting in a tendency towards earlier sleep relative to circadian phase. BP usually decreases during sleep and this appears protective as there is an association between a <10% drop in the nocturnal vs. daytime BP (the so-called non-dipping BP) and more adverse CV events and mortality. Blacks have increased prevalence of this dangerous non-dipping 24-h BP fluctuation. Recently, we discovered a robust endogenous circadian rhythm in BP, unrelated to activity or sleep, with a circadian drop in BP across the biological night that likely contributes to nocturnal BP dipping. The diurnal variation in BP is the result of a summation of the effects on BP of varied behaviors across the day and night (e.g., sleep, waking up, exercise, other stresses) and the effects on BP of the circadian system. We plan to examine these interacting factors in 26 Black and 26 White adults, aged 40-60 years, to determine sleep and circadian mechanisms that may contribute to higher overall BP and reduced nocturnal drop in BP in Blacks. This will be achieved by using an intensive multi-day protocol where sleep-wake cycles are adjusted to 20-h so all behaviors occur evenly across all circadian phases while in a constant dim light (to avoid light resetting circadian phase). Sleep will be assessed with polysomnography and circadian phases by core body temperature. By studying standardized behaviors and regulators of BP during sleep and behavioral stresses across all circadian phases, this protocol will allow us to determine if the higher overall BP and reduced nocturnal drop in BP in Blacks compared to Whites is due to poor sleep, while controlling for circadian phase (Aim 1); reduced BP responses to standardized behavioral changes across the day and night (such as less reduction in BP during slow-wave sleep and/or reduced post-exercise hypotension; Aim 2); or reduced circadian amplitude of BP (Aim 3). Socioeconomic status and history of stress exposures will be adjusted for in all analyses. This study will be the first to distinguish the contributions of sleep, circadian and behavioral mechanisms to the non-dipping BP profile in Blacks and lay the groundwork for optimizing therapies dependent on mechanisms, such as targeting sleep, circadian rhythmicity, or behaviors, and raising the possibility that ideal therapy for HTN may differ by race. This research will ultimately help to improve health and survival in black populations with HTN.